Search

Aim: The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC)., Patients and Methods: Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73%) with three cycles of cisplatin (100 mg/m(2), every 3 weeks) or BRT (n = 71; 27%) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005)., Results: Median follow-up was 29 months. In all, 56% of patients treated with CRT received the planned three cycles (92% at least two cycles) and 79% patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72% and 61%, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79%, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76% for CRT vs. 61% for BRT) and DC (2-year LRC: 81% for CRT vs. 68% for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001)., Conclusion: This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.

Purpose: To determine the maximum tolerated dose (MTD) of oral cisplatin (CP Ethypharm®) in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC) and the recommended dose for phase II trials., Patients and Methods: Phase I, multicenter, open-labelled, non-comparative and dose escalating trial. CP Ethypharm® was administered on five consecutive days every other week for 7 weeks (4 treatment cycles) in combination with radiotherapy. Eighteen patients with locally advanced HNSCC were allocated to four cisplatin dose levels: 10 mg/m(2)/day: 4 patients; 15 mg/m(2)/day: 4, 20 mg/m(2)/day: 5 and 25 mg/m(2)/day: 5. The inclusion of patients was dictated by occurrence of dose limiting toxicities (DLTs) at each dosing level., Results: The most frequently experienced AEs were gastrointestinal (GI) disorders. Five DLTs were observed, including three at 25 mg/m(2) level (two grade 2 renal toxicities, one grade 3 GI and renal toxicities), one at 20 mg/m(2) level (grade 3 GI disorders), one at 10 mg/m(2) level (grade 4 mucositis). PK analysis showed no significant difference of C(max) values between day 1 and day 5 of treatment at each dose level (total & ultrafilterable platinum)., Conclusion: Due to 3 DLTs experienced at 25 mg/m(2)/day, MTD was reached and the recommended dose for phase II studies was determined as 20 mg/m(2)/day., (Copyright © 2010. Published by Elsevier Ireland Ltd.)

A phase I-II study was initiated in February 1991 of concomitant radiation and cisplatin (CDDP) in the treatment of unresectable head and neck squamous cell carcinomas (n = 12). The first patient was treated palliatively for a cervical recurrence of laryngeal cancer. The 11 other patients had locally advanced (stage IV) previously untreated carcinomas of the oropharynx (n = 9), hypopharynx (n = 1), or cervical node with unknown primary site (n = 1). Standard external radiation was carried out up to a total dose of 60 Gy/6 weeks (7 MeV electron beam) for the first patient and 72 Gy/8 weeks (Co60 beam) for the other 11 patients. CDDP was infused continuously during the entire radiation treatment, 5 days/week. The starting dose was 4 mg/m2/day and was escalated by increments of 1 mg/m2/day; dose-limiting toxicity was observed at 7 mg/m2/day. Neutropenia (grade 4, one patient; grade 3, three patients) and thrombocytopenia (grade 3, one patient; grade 2, one patient) were the limiting factors. Therefore, the recommended dose of CDDP is 6 mg/m2/day. All patients but one completed the scheduled radiation. For the entire group, mucositis was not more severe than that observed with radiotherapy alone. There was no nephro-, oto-, or neurotoxicity. A complete response was obtained in eight (66%) patients. Of these, four were free of disease 12-34 months after completion of treatment and one had a total glossectomy for a tongue necrosis. For the whole series, the mean overall survival was 16 months posttreatment. Pharmacokinetic analysis indicated the total cisplatin accumulation at the end of treatment to be 743-1551 ng/ml. Accumulation of ultrafilterable platin was noted in only one patient (137 ng/ml at the end of treatment).

Purpose: To report the final results of a prospective randomized trial that aimed to evaluate efficacy and toxicity of concomitant postoperative radiotherapy and Cisplatin infusion in patients with Stage III or IV squamous cell carcinoma of the head and neck and histological evidence of extracapsular spread of tumor in lymph node metastase(s)., Methods and Materials: Radiotherapy was delivered using a daily dose of 1.7 Gy for the first 54 Gy and 1.8 to 2 Gy until the completion of the treatment. Cisplatin 50 mg i.v. with forced hydratation was given or not every week (i.e., seven to nine cycles) concurrently with radiotherapy. A total of 44 patients were treated by irradiation only (RT group) and 39 by irradiation with chemotherapy (CM group)., Results: The RT group displayed a higher rate of loco-regional failures as compared to CM group (41 vs. 23%; p = 0.08). The overall survival, the survival corrected for deaths by intercurrent disease, and the disease-free survival were better in CM group as compared to RT group with statistically significant differences. Survival without loco-regional treatment failure was better in the CM group, the difference being close to the level of significance (p = 0.05). Survival without distant metastases were comparable in the two therapeutic groups. Ten severe late complications were observed, four in the RT group (17%) and six in the CM group (22%). Cox univariate analysis confirmed the importance of the therapeutic modality in predicting the overall survival, the survival corrected for deaths by intercurrent disease, and the disease-free survival., Conclusions: The present final report of this phase III study confirms preliminary results. The concomitant use of 50 mg weekly Cisplatin infusion and postoperative radiation improved loco-regional control and survival. No significant increase of late radiation complications was observed in the CM group.